- Delivery Method:
- VIA UNITED PARCEL SERVICE
- Medical Devices
Recipient NameMr. Jason Smith
Recipient TitleManaging Director
- Bedfont Scientific, Ltd.
- Issuing Office:
- Center for Devices and Radiological Health
February 12, 2020
Dear Mr. Smith:
During an inspection of your firm located in Maidstone, Kent, United Kingdom, on October 28, 2019 through October 31, 2019, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures carbon monoxide gas analyzers. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. §321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. §351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
We received a response from Ms. Louise Bateman, Quality and Regulatory Affairs Manager, dated November 20, 2019, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures for validating the device design, as required by 21 CFR 820.30(g). For example:
a. The design validation performed on September 21-22, 2016 and documented in the "Customer Usability Analysis" dated January 17, 2017, to demonstrate the ToxCO met user needs and intended use requirements, was performed on units that were not initial production units. The units tested included a firmware version prior to the version implemented. The transferred design used firmware (b)(4) which included several changes including changes to the general user interface based on the results of the Usability Analysis. Your firm has not documented how the devices used in that initial study are equivalent to initial production units or performed a new usability analysis to ensure the device with the updated firmware met customer needs and intended use.
The adequacy of your firm’s response cannot be determined at this time. Your firm’s Project Manager will ensure that all usability engineering reports include a rationale to state why the samples used are representative of production models. The Project Manager will review post market data to determine if any issues remain regarding the usability of the device. Any necessary actions will be handled in accordance with change control procedures. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
b. The approved ToxCO Product Requirement Specification, Document No. (b)(4), included new requirements Ref. Nos. (b)(4). However, no verification and/or validation tests have been performed for these new requirements.
The adequacy of your firm’s response cannot be determined at this time. Your firm’s Project Manager will carry out a verification and validation review to determine if the changes implemented have achieved the expected results. Verification and Validation Engineers will be trained on the importance of verification and validation testing following the implementation of changes. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
c. Software changes are not adequately documented following your firm’s change control procedure (b)(4). The Product/Process Change Request form FRM-01 was not initiated for the change of the firmware (b)(4) and (b)(4).
The adequacy of your firm’s response cannot be determined at this time. Your firm’s Project Manager will arrange for the appropriate documentation to be completed to ensure that a record of the change is held and will train engineers on the importance of recording and approving changes in accordance with procedures. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
2. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example:
a. Your firm’s analysis of quality data is inadequate. Your firm is unable to use its ticket system to trend appropriately by, but not limited to, products, problems/issues, component failures, or ticket categories, to detect recurring issues. There is no uniformity in how “Categories" are selected. Some tickets created for complaints are documented as “Service”, “Repairs”, or “Supplier Fault”. Some records indicate products as “Other”, but further review of the records indicates a product name, multiple products, or components of a product.
The adequacy of your firm’s response cannot be determined at this time. Your firm’s QA/RA Manager will review the software with the designer to expand the categories to allow a more specific analysis; add additional category fields to provide a more granular analysis; or implement alternative software currently under review. Additional training will be carried out with the staff responsible for Category input to ensure they understand the purpose of this information and to give guidance to ensure the categories are more representative of the issue being recorded. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
b. Ticket #645492 was closed without a documented verification of CAPA effectiveness.
The adequacy of your firm’s response cannot be determined at this time. Ticket #645492 will be corrected to account for the need to document verification of CAPA effectiveness which will be included in your firm’s training. All other tickets will be reviewed to determine if they have the same issue. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
c. Ticket #305030 identified two problems with the Steribreath tubes: primary packages not sealing properly and larger diameter dimensions causing the accessory to not fit in the device. These problems were referred to your firm’s Steribreath supplier for investigation and corrective actions. However, the ticket was closed without addressing the tube dimension problem.
The adequacy of your firm’s response cannot be determined at this time. Ticket #305030 will be reopened to determine what corrective actions your firm’s supplier should take prior to conducting verification of CAPA effectiveness and closing out the ticket. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
3. Failure to establish and maintain procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). For example, one (b)(4) the CO and H2 Bump Tests. However, the results were (b)(4) released for distribution. Your firm does not require a review of test data to verify results.
The adequacy of your firm’s response cannot be determined at this time. A review of out of specification results will be carried out to determine if a field corrective action needs to take place or if the device can be released under concession. The results of the review and subsequent actions will be recorded including signatures and dates of the reviewers. Your firm will introduce requirements for the review of test results to verify if they meet specifications. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
4. Failure to ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results, as required by 21 CFR 820.72(a). For example:
a. Your firm has not established a procedure to provide specific directions and limits for accuracy and precision for the calibration of the flow meters.
The adequacy of your firm’s response cannot be determined at this time. Your firm’s Technical Manager will review the current process for the calibration of the gold standard device, ensuring accuracy when checking internal flow meters. The Technical Manager will document the process for the calibration of the flow meters and conduct training. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
b. No action was taken when test equipment was found to not meet accuracy and/or precision limits to evaluate whether there was any adverse effect on the device's quality. The calibration record for the flow meters performed on September 20, 2019, showed 15 flow meters failed calibration, and the calibration record for the flow meters performed on September 18-19, 2018, showed 2 flow meters failed calibration. Your firm has not adequately implemented its calibration program procedure (b)(4) in that no assessment is documented following (b)(4) to assess the impact on products that may have been tested using those flow meters as required by (b)(4).
Your response is not adequate. The flow meters were removed from the Research and Development department to ensure they were not used in the release of product. Your firm’s Technical Manager will document the failures and the results of the investigation into flow meter use and conduct training for all staff involved in the calibration of flow meters on procedural requirements. Your response did not provide information to ensure the flow meter accuracy and precision limits would be reestablished and an evaluation as to whether there was an adverse effect on the quality of the devices tested with these out of calibration flow meters. Additionally, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
5. Failure to establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example, your firm has not adequately implemented its quality audit procedure (b)(4) in that (b)(4) of 24 areas of the Quality System were not audited in 2017 and 9 out 23 areas were not audited in 2018.
The adequacy of your firm’s response cannot be determined at this time. Your firm’s QA/RA Manager will create a revised audit schedule and allocate additional resources where necessary to ensure on-time completion. Management will be notified of further incidents of unplanned audits to enable the addition of resources as necessary. However, documentation of these activities has not been provided for review and you have not provided a timeline for the proposed corrective actions.
U.S. federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been corrected. Also, should FDA determine that your devices do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted. More information on processes for persons denied a CFG can be found at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-request-review-fdas-decision-not-issue-certain-export-certificates-devices. If you believe that your products are not in violation of the Act, please respond to FDA with your reasoning and any supporting information for our consideration.
Please notify this office in writing, within fifteen business days from the date you receive this letter, of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm’s response(s) and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Regulatory Programs, Division of Regulatory Programs 2, FDA Inspections and Regulatory Audits Team, White Oak Building 66, Room 3540, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #604311 when replying. If you have any questions about the contents of this letter, please contact: Todd Courtney at +1(301)796-6371 (telephone).
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.
Malvina B. Eydelman, M.D.
OHT 1: Office of Ophthalmic, Anesthesia, Respiratory,
ENT and Dental Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
212 Cottage Grove Ave., Suite C
Santa Barbara, CA 93101